Conservative multimodal management of a primitive neuroectodermal tumor of the thyroid.

Primitive neuroectodermal tumors (PNET) represent 1% of sarcomas. Head and neck peripheral PNETs have an intermediate prognosis between abdominopelvic disease and extremities. We here report the case of a 40-year old male who presented with primitive neuroectodermal tumor of the thyroid and was treated by multimodal treatment, including surgery, chemotherapy and intermediate dose radiotherapy. The patient is alive and fit with a functional larynx at 27 months. Multimodal treatments yield five-year survival rates of about 60%. Major drug regimens use vincristine, doxorubicin, ifosfamide or cyclophosphamide, dactinomycin and/or etoposide. Complete surgical excision is undertaken whenever possible to improve long-term survival. However, the relative radiosensitivity of tumors of the Ewing family, suggest multimodal treatment including adjuvant conformal radiotherapy in case of positive margins or poor response to chemotherapy rather than resection with 2-3 cm margins, which would imply laryngeal sacrifice for thyroid tumors. The role of expert rare tumor networks is crucial for optimal decision-making and management of such rare tumors on a case by case basis.

The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands.

OBJECTIVE: To investigate the role of radiation therapy in rare salivary gland pediatric mucoepidermoid carcinoma (MEC). STUDY DESIGN: A French multicenter retrospective study (level of evidence 4) of children/adolescents treated for MEC between 1980 and 2010 was conducted. RESULTS: Median age of the 38 patients was 14 years. Parotid subsite, low-grade, and early primary stage tumors were encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient were treated by tumoral surgical excision, and 53% by neck dissection (80% of high grades). Postoperative radiation therapy and chemotherapy were performed in 29% and 11% of cases. With a median 62-month follow-up, overall survival and local control rates were 95% and 84%, respectively. There was 1 nodal relapse. Lower grade and early stage tumors had better survival. Postoperative radiation therapy and chemotherapy were associated with similar local rates. Patients with or without prior cancer had similar outcomes. CONCLUSIONS: Pediatric salivary gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors should be treated with surgery alone. Neck dissection should be performed in high-grade tumors. Radiation therapy should be proposed for high grade and/or advanced primary stage MEC. For high-grade tumors without massive neck involvement, irradiation volumes may be limited to the primary area, given the risk of long-term side effects of radiation therapy in children. Pediatric MEC as second cancers retain a similar prognosis. Long-term follow-up is needed to assess late side effects and second cancers.

[Salivary gland tumors in children]. / Tumeurs malignes des glandes salivaires chez l'enfant.

Salivary gland tumors in children are rare: they correspond to 8-10% of head and neck pediatric tumors. Clinicians of all disciplines should be aware of this diagnosis in front of non-inflammatory mass of the parotid or in the territory of other salivary glands. In children, 50% of salivary gland tumors are malignant which contrasts with a 10-25% risk in adults. Epithelial tumors are the most common, mucoepidermoïd carcinomas of the parotid in particular. Surgery is the treatment of choice in epithelial tumors. Adjuvant radiotherapy may be indicated in case of unfavorable prognostic factors but must be balanced with the risk of radiation-induced growth defects and secondary cancer. The role of chemotherapy is limited in these tumors, but should be discussed in case of an inoperable or metastatic lesion.

Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

OBJECTIVE: To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma. DESIGN: Multicenter, retrospective study. SETTING: Eleven French hospitals. PATIENTS: The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only. MAIN OUTCOME MEASURES: Survival rates, disease recurrence, and postoperative complications. RESULTS: The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively. CONCLUSION: The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.

Primary cancer of the sphenoid sinus--a GETTEC study.

BACKGROUND: Primary involvement of the sphenoid sinus occurs in 2% of all paranasal sinus tumors and is associated with dismal prognosis. Optimal management remains debatable. METHODS: A total of 23 patients were treated for a primary cancer of the sphenoid sinus from 1988 to 2004. Charts were reviewed for patient-, tumor-, and treatment-related parameters. Univariate and multivariate analyses were conducted to identify prognostic factors for locoregional control and survival. RESULTS: Cranial neuropathies were present in 12 patients. Pathologic findings included adenoid cystic carcinoma, adenocarcinoma, lymphoma, squamous cell carcinoma, sarcoma, neuroendocrine carcinoma, melanoma, and malignant hemangiopericytoma. All but 2 patients had stages III to IV cancer. Radiotherapy was performed in 18 patients and chemotherapy in 12. Of 10 patients undergoing surgery, total excision with grossly negative margins was achieved in 4 patients and subtotal resection in 6. Median locoregional control and overall survival were 12 and 41 months, respectively. On multivariate analysis, cranial neuropathy was associated with worse locoregional control and survival. Surgery was rarely complete because of advanced stages at presentation, but it yielded better outcomes than other treatments without surgery in non lymphoma-cases. CONCLUSION: Early CT and MRI should be performed when facing aspecific, rhinological, or neuro-ophtalmological symptoms. Cranial neuropathies indicate a worse prognosis. Surgery, including debulking surgery, may be preferred to combined modality treatments without surgery. Its apparently favorable impact on prognosis would need to be tested in homogenous histological groups of patients, which is impossible because of the rarity of the disease. Highly conformal radiotherapy (adjuvant or definitive) should be encouraged and optimized with concurrent chemotherapy in advanced stages. Aggressive multidisciplinary management including surgery, chemotherapy, and radiotherapy should be encouraged and adapted on histology and tumor extensions. Progress is still warranted to improve outcomes.

Need for neck dissection after radiochemotherapy? A study of the French GETTEC Group.

BACKGROUND/HYPOTHESIS: The need for a neck dissection after radiochemotherapy (RCT) for patients with unresectable cancer of the head and neck remains questionable. We evaluated our strategy to perform a neck dissection in patients with a controlled primary tumor based on the response to RCT according to regional control, survival rates, and morbidity. STUDY DESIGN: The French "Groupe d'Etude des Tumeurs de la Tête et du Cou" (GETTEC) group retrospectively performed a multicenter review. One hundred and three stage III (N = 7) or IV (N = 96) patients with unresectable primary tumors and node-positive disease and no distant metastases treated between 1996 and 2002. Tumors were considered unresectable or with poor surgical curability based on advanced stage, or patients were surgically unfit for medical reasons. RESULTS: With a median follow-up of 30 months, the complete clinical and radiological nodal response rate was 61%. Among 39% (N = 40) of patients with residual neck disease, 70% (N = 28) underwent a neck dissection, whereas the remaining 30% either underwent watchful follow-up for probable scary nodes, or were deemed unresectable or medically unfit for surgery. Half of the neck dissection specimens showed pathological evidence of viable tumor. Grade 3 to 4 complications were recorded in four patients (14%) after neck dissection. Regional control was better for complete responders. Disease-free survival and overall survival were similar between patients with a complete response in the neck and no neck dissection, and patients with a neck dissection for residual neck disease. CONCLUSIONS: The strategy to avoid a neck dissection is safe in patients with a complete response in the neck, regardless of initial nodal stage. In patients with residual neck disease, postRCT neck dissection can be performed with limited morbidity. Progress is warranted to optimize the pathological response in the nodes and to better assess ambiguous nodal responses with multi-modal imaging.

Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

OBJECTIVE: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature. MATERIALS AND METHODS: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease. RESULTS: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series. CONCLUSION: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.

Squamous cell carcinoma of the nasal columella: a retrospective study of 66 cases from the GETTEC.

Squamous cell carcinoma of the nasal columella (SCCNC) is a rare disease. We aimed to define a strategy for the diagnosis and management of nasal columella squamous cell carcinoma. Medical records of 66 patients presenting with columella squamous cell carcinoma in nine French hospitals, from 1980 to 2003, were evaluated to determine the clinical characteristics and current treatment of the disease. Mean age was 69 years. The sex ratio was one female for three males. Majority of the lesions were T1 N0 according to the classification international union against cancer. Patients underwent one of the three treatments: surgery alone for the T1 lesions, radiotherapy for tumors of T2-T3 and combined (surgery and radiotherapy) for T4 lesions. The 5-year Kaplan-Meier survival test was 39% and no difference was found between the therapeutic groups. Thirty-five (53%) tumor recurrences were observed with a median time of 43 months. As regards TNM classification and treatment, no significant difference between the two groups disease free/recurrence was found. Prognosis of early lesions was considered better than the advanced lesions. SCCNC is difficult to manage and has a poor prognosis. No therapeutic solution has yet been confirmed in the treatment of this pathology.

Ferumoxtran-10 enhancement in orthotopic xenograft models of human brain tumors: an indirect marker of tumor proliferation?

PURPOSE: Ferumoxtran-10 belongs to the Ultra Small Particles of Iron Oxide (USPIO) class of contrast agents and induces delayed tumor enhancement in brain tumors, reflecting the trapping of iron oxide particles by the macrophages and activated microglia. The aim of the study was to compare Ferumoxtran-10 contrast enhancement in four human high-grade glioma xenograft models (TCG2, TCG3, TCG4, and U87) with different growing profiles. MATERIALS AND METHODS: Fragments of human malignant glioma were orthotopically xenografted into the brain of four groups of nude mice. All mice underwent a MRI examination 24 h after intravenous administration of Ferumoxtran-10 (axial T1 SE weighted MR images). The contrast enhancement observed in the different tumor types was measured and was correlated to in vivo tumor growth and to histological parameters, such as proliferative tumor cell fraction, apoptosis, vascular density, and Perls' staining score. RESULTS: A good relationship was observed: (a) between tumor-to-background contrast and proliferative index, (b) between tumor-to-background contrast and tumor growth, and (c) between tumor-to-background contrast and Perls' staining score. The registered MR enhancement contrasts were not influenced by apoptotic index and by vascular density in these experimental xenografts. CONCLUSIONS: Tumor contrast enhancement 24 h after intravenous Ferumoxtran-10 administration seems to be well correlated to tumor proliferative index and tumor growth and could be used as an indirect marker of tumor proliferation.

Mucoepidermoid carcinoma of salivary glands in the pediatric age group: 18 clinical cases, including 11 second malignant neoplasms.

BACKGROUND: Salivary gland tumors represent 1% of head and neck tumors, with only 5% of these occurring in patients younger than 20 years. Mucoepidermoid carcinoma (MEC) is one of the most frequent salivary gland cancers among adults and children. METHODS: This survey was conducted among 34 French pediatric oncology departments. From 1980 to 2000, 18 cases were reported. RESULTS: Treatment included surgery or radiotherapy, or both. The 5-year survival rate was 93.7%. Eleven patients had been previously treated by radiotherapy and/or chemotherapy for a first malignant tumor, specifically, lymphoid leukemia (n = 4), lymphoma (n = 3), brain tumor (n = 2), sarcoma (n = 1), and retinoblastoma (n = 1). CONCLUSIONS: MEC is very rare in the pediatric age group. Treatment involves surgical removal of the tumor plus radiotherapy, according to histologic staging. MEC has a good prognosis in young patients. The survival rate does not differ in the subgroup of patients with MEC as a secondary tumor.

Wild-type p53 gene transfer into mutated p53 HT29 cells improves sensitivity to photodynamic therapy via induction of apoptosis.

Photodynamic therapy (PDT) is an effective local cancer treatment that induces cytotoxicity through the intracellular generation of reactive oxygen species. It is generally thought that p53 regulates chemotherapy and radiation therapy responsiveness via apoptosis induction control. The current study investigated whether cellular sensitivity to PDT is increased when a wild-type (wt) p53 status is restored by gene transfer in the established HT9blk Ala273-mutant p53 human colon cancer cell line. The photosensitizer accumulation was similar in both cell lines, and survival measurements using MTT test and clonogenic assays demonstrated that wt p53 transfected cells (HT29A4) were significantly more sensitive to chlorin e6-mediated PDT. P53 protein expression and its functionality as a transcription factor demonstrated through the induction of mdm2 transactivation, were not found to be directly involved in this differential photosensitivity. However, induction of caspase 3 activation (2.6-fold), leading to significant apoptosis induction 24-h after PDT was observed in HT29A4 cells. These results suggest that the introduction of wt p53 in HT29A4 potentiates the cell sensitivity to PDT through the induction of apoptosis in relation to p53 mutational status, but independently of p53 expression level and transcriptional activity.